Blinatumomab approved as consolidation therapy for MRD-negative B-cell precursor acute lymphoblastic leukemia

The addition of blinatumomab to consolidation chemotherapy significantly improves overall survival for adult patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) who show no trace of cancer after achieving complete remission with induction chemotherapy according to a study by the ECOG–ACRIN Cancer Research Group published in The New England Journal of Medicine.¹

The finding represents another practice-changing role for blinatumomab in BCP-ALL. On June 14, 2024, the US Food and Drug Administration (FDA) approved the addition of blinatumomab to consolidation chemotherapy for patients with BCP-ALL who show no measurable residual disease (MRD) after achieving complete remission with induction chemotherapy.² This approval follows the approval for MRD-positive BCP-ALL in 2018 and the initial approval for relapsed/refractory BCP-ALL in 2014.^{3, 4}

The latest finding is from the phase 3 E1910 study, in which 488 patients aged 30–70 years with BCP-ALL were enrolled and treated with two cycles of induction chemotherapy. Of the participants, 244 achieved complete remission with no MRD (assessed by flow cytometry and defined as <0.01% leukemic cells in bone marrow), and they were randomized 1:1 to four cycles of either blinatumomab plus consolidation therapy or consolidation therapy alone.

At 3 years, significant improvement in overall survival was seen in the patients treated with blinatumomab versus those treated with consolidation therapy alone (85% vs. 68%, p = .002), with a benefit also seen in relapse-free survival (80% vs. 64%). The most benefit was seen in patients aged 30–55 years, with 3-year overall survival rates of 95% and 70%, respectively, and relapse-free survival rates of 87% and 70%, respectively.

“These results have never been seen before,” says the lead author of the study, Mark R. Litzow, MD, a professor of medicine in the Division of Hematology at the Mayo Clinic in Rochester, Minnesota. Dr Litzow emphasizes the importance of this finding for patients with no MRD, as these patients still can suffer a recurrence or relapse despite their good prognosis.

Commenting on the study, Nicholas Short, MD, an associate professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, Texas, acknowledges the practice-changing findings of this study and others that have led to FDA-approval of blinatumomab for BCP-ALL regardless of MRD status, but he offers two caveats.

He notes that the backbone chemotherapy used in the study is not commonly used in clinical practice and is likely inferior to other commonly used regimens. “Therefore, the magnitude of benefit with blinatumomab when used with these other chemotherapy regimens remains unknown,” he says.

In addition, he cautions that it remains unknown what the benefits of blinatumomab are for patients with an MRD-negative status determined by more sensitive MRD assays, such as next-generation sequencing of immunoglobulin/T-cell receptor gene arrangements for MRD detection. “It remains unknown whether patients with rapid and deep MRD responses to initial chemotherapy will still significantly benefit from blinatumomab,” he says.